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Distinct regions of loss of heterozygosity on 22q at different sites of head and neck squamous cell carcinomas.
Patricia Pintor dos,
Rodrigo Mattos dos,
Med. Sci. Monitor 2002: 8 (3) s.BR89-BR94, il., tab., bibliogr. 31 poz.
Hasła klasyfikacyjne GBL:
Background: Frequent loss of heterozygosity (LOH) has been reported in many types of cancer, including head and neck carcinomas. Somatic deletions involving specific chromosomal regions are strongly associated with inactivation of the allele of a tumor suppressor gene located within the deleted region. In most studies concerning LOH in head and neck squamous cell carcinomas (HNSCC) the different anatomical sites are not distinguished. The behavior of tumors arising at various sites differs significantly, however, suggesting different intrinsic tumor propoerties. In this study we compared the LOH on 22q and its relationship to clinciopathological parameters at the three major sites of HNSCC: oral cavity, larynx and pharynx. Material/Methods: LOH and microsatellite instability (MSI) were studied using seven polymorphic microsatellite markers mapped to the 22q11-q13.3 region in 37 oral, 32 laryngeal, and 31 pharyngeal carcinomas. Results: Two separate regions of LOH were identified in the laryngeal (22q11.2-12.1) and oral cavity (22q13.1-13.31) tumors. When the different anatomical sites were compared, a statistically significant difference was found between the presence of LOH at D22S421 (p 0.001), D22S315 (p = 0.014) and D22S929 (p = 0.026) in the laryngeal tumors. Conclusions: These data suggest that distinct regions on 22q are involved in LOH in oral cavity and laryngeal tumorigenesis, but do not support a similar association between the development of pharyngeal tumors and genes located on 22q. These findings implicate the presence of different tumor suppressor genes maping to distinct regions on chromosome 22q in oral and layrngeal carcinomas.
Clinical and pharmacokinetic study of fractionated doses of oral etoposide in pediatric patients with advanced malignancies.
Med. Sci. Monitor 2002: 8 (9) s.PI70-PI77, il., tab., bibliogr. 31 poz.
Hasła klasyfikacyjne GBL:
dzieci 2-5 r.ż.
dzieci 6-12 r.ż.
dzieci 13-18 r.ż.
Background: The purpose of this phase I study was to evaluate the toxicity profile, dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and plasma pharmacokinetics of oral etoposide, and to recommend a safe fractionated dose for phase II trials in pediatric patients with refractory solid tumors. Material/Methods: All patients had tumors no longer amenable to established forms of treatment. The initial dose of etoposide was 20 mg/mý TID for 14 days every 21 days (dose-level I). Etoposide plasma pharmacokinetics were studied on day 1 of treatment and determined by PHLC. Results: Seventeen children were enrolled, 13 of whom were included in the pharacokinetic study, for a total of 64 courses. nine patients were included at dose-level I; grade 2-3 leucopenia was observed in 5. The dose was then raised to 25 mg/mý (dose-level II) in another 8 patients; grade 3-4 leucopenia was observed in 4. This dose-level was therefore considered the MTD. The DLT was neutropenia. In patients at dose-level I and II the maximum plasma etoposide concentration was 2.97 and 8.59 ćg/ml, respectively. Drug levels 1 ćg/ml were maintained for about 6.3 hours following drug administration at both dose-levels. Partial response was observed in 1 patient and 4 patients showed stable disease. Conclusions: Prolonged oral etoposide was well tolerated by our patients. Considering the MTD, and fact that the patients included at dose-level I achieved an adequate ( 1 ćg/ml) plasma concentration of etoposide for a sufficient time, this dose level was recommended for phase II studies in pediatric malignancies...
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